Scarring, or scar formation, is a reactive condition of connective tissue cells that occurs following surgery and traumatic injury, as well as in fibrosis associated with chronic diseases such as scleroderma. Studies of wound healing and scar formation have shown that several factors are present in elevated levels in fibrotic connective tissue, and in patients with fibrotic diseases such as scleroderma and keloids. Among these is connective tissue growth factor (CTGF), a secreted protein shown to promote the synthesis of extracellular matrix and connective tissue components (Frazier K et al., J Invest Dermatol 1996,107(3):404-11; Igarashi A et al., J Invest Dermatol 1995,105(2):280-4). Overexpression of CTGF in such conditions may contribute to the observed scarring. Another agent found to be up-regulated in scarring conditions is TGF-β.
Several anti-scarring drugs have been developed to target TGF-β , for example by blocking its activation with mannose-6-phosphate analogs, or by neutralizing its action with antibodies.
In the eye, stromal scarring is a major complication following corneal trauma, infection or refractive surgical procedures such as RK. At present, there are no agents that are proven to clinically reduce corneal scarring without causing serious side effects. The use of steroids is prohibited in many instances of infection and has not been shown to be of benefit in controlled studies of PRK. Other agents that have been proposed for clinical use to reduce corneal scarring include drugs such as 5-fluorouracil, mitomycin C, interferon-γ , cyclosporin A, and a synthetic inhibitor of matrix metalloproteinases. However, powerful, nonspecific anti-cancer drugs can cause serious side effects such as persistent epithelial defects and endothelial damage, and the other drugs have not been tested in clinical trials.
There is a great need to develop agents that selectively inhibit scarring without producing serious side effects.